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It remains poorly understood whether CRF or adiposity accounts for a greater amount of variation in measures of brain health. We examined the contribution of CRF, adiposity, and their interaction with hippocampal structure. This study included 124 sedentary adults (<jats:italic>M<\/jats:italic>\u00a0=\u00a044.34) with overweight\/obesity (Body Mass Index mean\u00a0=\u00a032.43). FMRIB\u2019s Integrated Registration and Segmentation Tool was used to segment the hippocampus. Using hierarchical regression, we examined whether CRF, assessed via a submaximal graded exercise test, or adiposity, assessed as percent body fat using dual\u2010energy x\u2010ray absorptiometry (DXA) was associated with left and right hippocampal volume. Vertex\u2010wise shape analysis was performed to examine regional shape differences associated with CRF and adiposity. Higher CRF was significantly associated with greater left hippocampal volume (<jats:italic>p<\/jats:italic> = .031), with outward shape differences along the surface of the subiculum and CA1 regions. Adiposity was not associated with left or right hippocampal volume or shape. The interaction between adiposity and CRF was not significant. Neither CRF nor adiposity were associated with thalamus or caudate nucleus volumes or shapes, two control regions. Higher CRF, but not adiposity, was related to greater left hippocampal volume, with outward shape differences along the surface of the subiculum and CA1 regions in a midlife sample with overweight\/obesity. These findings indicate that, within the context of obesity, CRF is an important contributor to hippocampal structure, highlighting the importance of interventions targeting CRF.<\/jats:p>","DOI":"10.1111\/psyp.13591","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T19:34:25Z","timestamp":1588275265000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The fitness versus body fat hypothesis in relation to hippocampal structure"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8597-2022","authenticated-orcid":false,"given":"Sarah L.","family":"Aghjayan","sequence":"first","affiliation":[{"name":"Department of Psychology University of Pittsburgh Pittsburgh PA USA"},{"name":"Center for the Neural Basis of Cognition University of Pittsburgh Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie C.","family":"Peven","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Pittsburgh Pittsburgh PA USA"},{"name":"Center for the Neural Basis of Cognition University of Pittsburgh Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2672-7374","authenticated-orcid":false,"given":"Chelsea M.","family":"Stillman","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Pittsburgh Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer C.","family":"Watt","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Pittsburgh Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirk I.","family":"Erickson","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Pittsburgh 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